Hydroxamates: Relationships between Structure and Plasma Stability

被引：94
作者：
Flipo, Marion [1 ,3 ,4 ]
Charton, Julie [1 ,3 ,4 ]
Hocine, Akila [1 ,2 ,3 ,4 ]
Dassonneville, Sandrine [1 ,2 ,3 ,4 ]
Deprez, Benoit [1 ,2 ,3 ,4 ]
Deprez-Poulain, Rebecca [1 ,2 ,3 ,4 ]
机构：
[1] Univ Lille Nord France, INSERM, Biostruct & Drug Discovery U761, F-59006 Lille, France
[2] Univ Lille Nord France, Fac Pharm, F-59006 Lille, France
[3] Inst Pasteur, IFR 142, F-59021 Lille, France
[4] PRIM, F-59006 Lille, France
来源：
JOURNAL OF MEDICINAL CHEMISTRY | 2009年 / 52卷 / 21期
关键词：
HISTONE DEACETYLASE INHIBITORS; MATRIX-METALLOPROTEINASE INHIBITORS; CONVERTING-ENZYME INHIBITORS; CANCER CELLS; POTENT; ACID; DISCOVERY; SERIES; DERIVATIVES; METABOLISM;
D O I：
10.1021/jm900648x
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Hydroxamates are valuable tools for chemical biology as well its interesting leads for medicinal chemistry. Although many hydroxamates display nanomolar activities against metalloproteases, only three hydroxamates have reached the market, among which is the HDAC inhibitor vorinostat. Failures in development are generally attributed to lack of selectivity, toxicity, or poor stability. To help medicinal chemists with respect to plasma stability, we have performed the first and preliminary study on structure-plasma stability for hydroxamates. We define some structural rules to predict or improve the plasma stability in the preclinical stage.
引用
收藏
页码：6790 / 6802
页数：13
相关论文
共 40 条
  • [1] Synthesis and structure-activity relationships of β- and α-piperidine sulfone hydroxamic acid matrix metalloproteinase inhibitors with oral antitumor efficacy
    Becker, DP
    Villamil, CI
    Barta, TE
    Bedell, LJ
    Boehm, TL
    DeCrescenzo, GA
    Freskos, JN
    Getman, DP
    Hockerman, S
    Heintz, R
    Howard, SC
    Li, MH
    McDonald, JJ
    Carron, CP
    Funckes-Shippy, CL
    Mehta, PP
    Munie, GE
    Swearingen, CA
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 2005, 48 (21) : 6713 - 6730
  • [2] Discovery and refinement of a new structural class of potent peptide deformylase inhibitors
    Boularot, Adrien
    Giglione, Carmela
    Petit, Sylvain
    Duroc, Yann
    de Sousa, Rodolphe Alves
    Larue, Valery
    Cresteil, Thierry
    Dardel, Frederic
    Artaud, Isabelle
    Meinnel, Thierry
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 2007, 50 (01) : 10 - 20
  • [3] Synthesis and structure-activity relationships of second-generation hydroxamate botulinum neurotoxin A protease inhibitors
    Capkova, Katerina
    Yoneda, Yoshiyuki
    Dickerson, Tobin J.
    Janda, Kim D.
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2007, 17 (23) : 6463 - 6466
  • [4] Synthesis and Modeling of New Benzofuranone Histone Deacetylase Inhibitors that Stimulate Tumor Suppressor Gene Expression
    Charrier, Cedric
    Clarhaut, Jonathan
    Gesson, Jean-Pierre
    Estiu, Guillermina
    Wiest, Olaf
    Roche, Joelle
    Bertrand, Philippe
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 2009, 52 (09) : 3112 - 3115
  • [5] A series of potent and selective, triazolylphenyl-based histone deacetylases inhibitors with activity against pancreatic cancer cells and Plasmodium falciparum
    Chen, Yufeng
    Lopez-Sanchez, Miriam
    Savoy, Doris N.
    Billadeau, Daniel D.
    Dow, Geoffrey S.
    Kozikowski, Alan P.
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 2008, 51 (12) : 3437 - 3448
  • [6] 5,5-dimethyl-1,4,2-dioxazoles as versatile aprotic hydroxamic acid protecting groups
    Couturier, M
    Tucker, JL
    Proulx, C
    Boucher, G
    Dubé, O
    Andresen, BM
    Ghosh, A
    [J]. JOURNAL OF ORGANIC CHEMISTRY, 2002, 67 (14) : 4833 - 4838
  • [7] Enhanced pharmacodynamic and antitumor properties of a histone deacetylase inhibitor encapsulated in lipsomes or ErbB2-targeted immunoliposomes
    Drummond, DC
    Marx, C
    Guo, ZX
    Scott, G
    Noble, C
    Wang, DH
    Pallavicini, M
    Kirpotin, DB
    Benz, CC
    [J]. CLINICAL CANCER RESEARCH, 2005, 11 (09) : 3392 - 3401
  • [8] Stability studies of vorinostat and its two metabolites in human plasma, serum and urine
    Du, Lihong
    Musson, Donald G.
    Wang, Amy Qiu
    [J]. JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, 2006, 42 (05) : 556 - 564
  • [9] Novel selective inhibitors of the zinc plasmodial aminopeptidase PfA-M1 as potential antimalarial agents
    Flipo, Marion
    Beghyn, Terence
    Leroux, Virginie
    Florent, Isabelle
    Deprez, Benoit P.
    Deprez-Poulain, Rebecca F.
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 2007, 50 (06) : 1322 - 1334
  • [10] A new simple and high-yield synthesis of suberoylanilide hydroxamic acid and its inhibitory effect alone or in combination with retinoids on proliferation of human prostate cancer cells
    Gediya, LK
    Chopra, P
    Purushottamachar, P
    Maheshwari, N
    Njar, VCO
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 2005, 48 (15) : 5047 - 5051
1234